A PROSPECTIVE PHASE II STUDY OF PEGASPARGASE‐COEP PLUS RADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED EXTRA‐NODAL NK/T‐CELL LYMPHOMA

Abstract

Introduction: The optimal first-line treatment for extra-nodal NK/T-cell lymphoma (ENKTL) has not been well-defined. This study aimed to evaluate the efficacy and safety of pegaspargase, cyclophosphamide, vincristine, etoposide and prednisone (COEPL) regimen combined with radiotherapy for patients with newly diagnosed ENKTL. Methods: Our study is a prospective, open-label clinical trial. Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. For patients with stage I/II nasal type ENKTL, treatment included 2-3 cycles of induction COEPL (cyclophosphamide 750mg/m2 day 1; vincristine 1.4mg/m2 day 1; etoposide 60mg/m2 days 1-3; prednisone 100mg days 1-5; pegaspargase 2500IUmg/m2 day 2, every 21 days) followed by concurrent chemoradiotherapy (e.g. RT ≥50Gy with concurrent 1-2 cycles of LOP regimen: pegaspargase, vincristine and prednisone every 14-21 days, with the same doses as described above), then by 1-2 cycles of COEPL regimen as consolidation. For patients with stage III/IV or extra-nasal ENKTL, treatment included 6 cycles of COEPL regimen with or without radiotherapy to local sites, and autologous stem cell transplantation was given in selected patients. Results: A total of 80 patients were enrolled. The median age was 41 years (range, 15-76 years). Sixteen patients (20%) had stage III/IV disease, 6 (8%) presented with extra-nasal ENKTL, and 10 (12.5%) had a PINK score ≥2. Complete response and overall response rates were 75.0% and 87.0%, respectively. With a median follow-up of 41.4 months (range 2.7-76.2 months), the 3-year progression-free survival (PFS) and overall survival (OS) rates were 71.3% (95%CI 61.1-81.5%) and 73.3% (95%CI 63.1-83.5%), respectively. For patients with stage I/II nasal type ENKTL (n = 62), the 3-year PFS and OS were 78.1% and 81.2%, respectively. For patients with stage III/IV or extra-nasal ENKTL (n = 18), 3-year PFS and OS were 48.1% and 45.7%, respectively. Major grade 3-4 adverse events were anemia (21.3%), leucopenia (18.8%), neutropenia (13.8%), thrombocytopenia (7.6%) and transaminase elevation (3.8%). No treatment-related death was observed. Conclusions: Pegaspargase-COEP chemotherapy in combination with radiotherapy is highly effective and safe for patients with newly diagnosed ENKTL. Keywords: chemotherapy; T-cell lymphoma (TCL).